Switching to Tirzepatide 5 mg from GLP-1 RAs: Clinical Expectations in the First 12 Weeks of Treatment

What were the changes in glycemic outcomes, body weight (BW) and adverse event (AE) occurrence in the first 12-weeks following a switch from GLP-1 RA to tirzepatide 5 mg, omitting 2.5-mg initiation dose?

Methods: This open-label study included participants of≥18yrs with type 2 diabetes (T2D), HbA1c≥6.5% to≤9.0%, and body mass index (BMI)≥25 kg/m^2 who were on a stable treatment dose of GLP-1 RAs for≥3 months (liraglutide 1.2 or 1.8 mg once daily, dulaglutide 0.75, 1.5, 3, or 4.5 mg once weekly [QW], or injectable semaglutide 0.5, 1, or 2 mg QW). Tirzepatide 5 mg QW was initiated for 12-weeks. The primary and secondary endpoints were change from baseline (CFB) in HbA1c and CFB in BW and glucose levels assessed by continuous glucose monitoring. Safety was also assessed.

Results: The efficacy analysis set (EAS) included 140 participants 58.3yrs on average, mean baseline HbA1c 7.39%, BMI 35.18 kg/m^2, duration of T2D ~12.4yrs and 55% female. GLP-1 RAs before switching included semaglutide, dulaglutide, and liraglutide (n=77, 59, 3). Mean HbA1c decreased from 7.39% to 6.96% after 12-weeks; mean CFB was -0.43% (p<0.001). Mean BW decreased from 100.42 kg to 98.27 kg, mean CFB was -2.15 kg (p<0.001). Significant changes from baseline in HbA1c and weight were observed in a subgroup analysis of baseline GLP-1 RAs, semaglutide and dulaglutide. At baseline, time above range (TAR,>180 mg/dL) was 22%, time in range (TIR, 71-180 mg/dL) 77%, and time below range (TBR,≤70 mg/dL) 1.1% while at Week-12 they were 15%, 83%, and 3.1% respectively. At Week-12, absolute TAR reduced by -7% (p<0.001); TIR, TBR increased by 6% (p<0.001) and 2% (p<0.05). In the GLP-1 RA subgroups, dulaglutide and semaglutide, TAR reduced (-9% and -7%, respectively; p<0.01) and TIR increased (6% and 5% respectively, p<0.05) while TBR did not change significantly from baseline. Participants (EAS, n=20) had gastrointestinal (GI) events which were mild (n=18) and moderate (n=2) in severity. Three participants discontinued tirzepatide due to AE. There were no deaths or incidences of severe hypoglycemia.

Conclusion: In this prospective study, when people with T2D on stable GLP-1 RA-treatment were switched directly and maintained on tirzepatide 5 mg, they experienced improved glycemic outcomes and additional weight reduction with an acceptable risk of GI AE over 12-weeks.

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Publication History

Article published online:
28 May 2025